Treatment of Hereditary Epidermolysis Bullosa: Updates and Future Prospects

Abstract

Epidermolysis bullosa (EB) represents a group of inherited blistering skin diseases, some forms of which are associated with considerable morbidity and increased mortality. Notably, in recessive dystrophic EB there can be extensive muco-cutaneous fragility and disease complications such as scars, contractures, anemia, malnutrition, and malignancy. Currently, there is no effective therapy or cure for EB. Over the last decade, however, a number of important advances have been made that are bringing new treatments closer to the clinic, including gene therapy, protein replacement therapy, cell therapies [allogeneic fibroblasts, mesenchymal stromal cells (MSCs), bone marrow stem cell transplantation, culturing/grafting revertant mosaic keratinocytes], gene editing/engineering, and clinical application of inducible pluripotent stem cells. Although a cure for EB still remains elusive, recent data on animal models and initial human clinical trials have raised the expectations of patients, clinicians, and researchers that disease modification and improved quality of life are feasible goals. Furthermore, the lessons learned in treating EB are likely to have significant implications for improving the management of other genetic diseases.

Esophageal Stenosis - a Notable Complication of Epidermolysis Bullosa - case report

“…In regards to new therapies, there are a few ideas that researchers are currently looking into such as gene therapy, protein replacement therapy or bone marrow stem cell therapy [6]. There is high hope that in the future, with the proper use of old and new medical approach, the patients with EB will have a better chance to a normal life and in the end a higher survival rate.…”

Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa

“…In this study, autologous keratinocytes were transduced with GMP grade gamma-RV containing fulllength COL7A1. Autologous epidermal sheets measuring ~35cm 2 (approximately the size of a playing card) were grafted onto 6 wounds in each of the patients. No serious adverse events were reported and there was C7 expression at the dermal-epidermal junction on graft sites in 90% of biopsies at 3 months, 66% of biopsies at 6 months and 42% at 12 months.…”

“…Depending on the level of blistering within the dermal-epidermal basement membrane zone, EB is classified into four main categories; simplex, junctional, dystrophic and Kindler syndrome (1). The sub-classification of EB extends to over 30 clinical subtypes with pathogenic mutations in at least 18 distinct genes (2). Within the spectrum of EB, ~ 5% of affected individuals have the clinically more severe recessive dystrophic (RDEB) variant.…”

Review of the 94th Annual Meeting of the British Association of Dermatologists, Glasgow 2014

“…Gene therapy is not the only potential management strategy for inherited disorders. 24 Options for recessive dystrophic epidermolysis bullosa include protein replacement with collagen VII and cell therapy with allogenic fibroblasts to aid wound healing. The latter is mediated via a paracrine effect, rather than production of normal protein by the fibroblasts.…”